EP2167026B1

EP2167026B1 - Cosmetic composition for treatment of canities

Info

Publication number: EP2167026B1
Application number: EP08760661.2A
Authority: EP
Inventors: Giammaria Giuliani; Anna Benedusi
Original assignee: Giuliani SpA
Current assignee: Giuliani SpA
Priority date: 2007-06-11
Filing date: 2008-06-06
Publication date: 2015-12-09
Anticipated expiration: 2028-06-06
Also published as: EP2005942A1; EP2167026A1; WO2008151994A1

Description

The present invention concerns the topical use of Khellin to reduce the amount of grey and white hair due to canities.
Khellin, or 4,9-dimethoxy-7-methyl-5H-furo[3,2-g][1]benzopyran-5-one is a derivative of coumarin which is known for its vasodilatory properties.
US4412071 (UpJohn ) describes khellin analogues indicated as anti-arteriosclerosis agents.
EP680761 (Indena ) relates to topical formulations based on khellin for cicatrizing the skin by means of its peripheral vasokinetic activity.
EP693278 (Indena ) relates to formulations against hair loss based on khellin, combined with unsaturated fatty acids, again utilizing its peripheral vasokinetic activity.
Khellin has also been studied for therapy of the skin disorder known as vitiligo, characterized by non-pigmented skin patches. In this regard, research has shown how the use of NB (narrow band) UVB is particularly effective in the treatment of said disease. Procaccini (Ann. Ital. Dermatol. Clin. Sper., 1993, 47, 4) reports that applying khellin topically would not in itself have a specific repigmentation action against vitiligo, any effective repigmentation action being essentially due to induction by UV rays.
According to the present invention, it has been surprisingly found that khellin for topical use is effective in reducing the amount of white hair due to canities without having to combine it with other agents such as UV light.
Principally to achieve this activity but also other advantages which will be described henceforth, the current invention presents a composition for cosmetic use able to reduce the amount of white hair due to canities, characterized by comprising khellin as the active principle and excipients that render it suitable for topical use on hair.
According to the present invention, khellin can be present as the only active principle in the composition or in combination with one or more additional active principles, chosen from phenylalanine, ornithine, catechin, quercetin, copper salts such as copper gluconate.
The composition of the invention can be prepared in the form of a possibly liposomal hair treatment mask, or shampoo, or lotion, or conditioner, or mousse. Preferably, in a composition according to the invention khellin is comprised in a quantity between 0.2 and 1.8% w/v. With the aim of better understanding the characteristics of the invention, nonlimiting examples of its practical implementation are described in the following.
The quantity of each of the components is expressed as percentage weight per volume, % w/v, or, in the case of lotions, as weight in grams per 100 ml.
In the examples, where indicated, the INCI names of the components are given in accordance with the International Nomenclature of Cosmetic Ingredients.

Example 1 - Liposomal hair mask

	Components	% w/v
1	Glycerin	3.00
5	Tween 20	1.00
6	Cremophor	0.30
7	Aristoflex	0.70
8	Phenonip	0.98
9	Copper gluconate	0.10
11	Cromollient SCE	3.00
13	Cremophor	0.60
14	Khellin	1.0-1.5
15	Phosal 75 SA	3.00
16	Parfum	0.60
17	Patent blue (0.2% solution)	0.30
18	Demineralized water	q.s. to 100 ml

Example 2 - Hair mask

	Components	% w/v
1	Corn starch	1.5
2	BC 2366	2.5
3	Disodium EDTA	0.2
4	Cetrimonium chloride	4
5	Salcare SC 92	2
6	Glycerin	4
7	Nexbase 2004	2
8	Fancol VB	1.5
9	BC 2262	0.5
10	Lanette O	1.5
11	Palm oil	0.8
12	Brij 721	1
13	Khellin	0.5-1.5
14	Crodazosoft DBQ	8
15	Cremophor RH 40	0.2
16	Tween 20	0.9
17	Glycerin	3.0
18	Incroquat behenyl tms	0.5-0.7
19	Cromollient SCE	0.6
20	Tween 20	0.1
21	Parfum	0.5
22	Phenonip	1
23	Water	q.s. to 100 ml

Example 3 - Shampoo

	Components	% w/v
1	EDTA	0.20
2	Polyquaternium-10	0.40
3	Sodium Lauroyl Sarcosinate	9.00
4	Magnesium laureth sulfate (75%) and Disodium laureth sulfosuccinate (25%)	38.00
5	Potassium Undecylenoyl Hydrolyzed wheat protein	1.00
6	PEG-40 Hydrogenated Castor Oil	0.50
7	Polysorbate 20	1.00
8	Cremophor RH 40	0.2
9	Tween 20	0.9
10	Glycerin	3.0
11	cromollient SCE	0.6
12	Prolipid 151	0.6
13	khellin	0.5-1.5
14	tween 20	0.3
15	cremophor RH40	6
16	Phenyltrimethicone & Silicone Quaternium-15	0.50
17	Silicone quaternium-15 & C11-15 Pareth-5 & C11-15 Pareth-9	0.80
18	Parfum 12144	0.60
19	BHA	0.01
20	Crodasilk liquid	1.00
21	Lauryl Methyl Gluceth-10 Hydroxypropyldimonium Chloride	0.50
22	Wheat (triticum vulgare) gliadins	1.00
23	Dore Gold AS232	0.05
24	Glycol Distearate, Laureth-7, Sodium Cocoamphoacetate, Cocamidopropyl Betaine and Sodium Laureth Sulfate	6.00
25	PEG-90 Glyceryl Isostearate (and) Laureth-2	1.20
26	PEG-120 Methyl Glucose dioleate	1.20
27	KCl	0.60
28	phenoxyethanol, methylparaben, butylparaben, ethylparaben, propylparaben	0.98
29	citric acid	0.50
30	Demineralized water	q.s. to 100.00

Example 4 - Hair lotion

	INGREDIENTS (INCI names)	g in 100 ml
1	Citric acid	0.04-0.052
2	Disodium EDTA	0.03-0.06
3	Alcohol	15-20
4	PEG-40 Hydrogenated castor oil	0.5-3
5	Tween 20	0.5-1.0
6	Parfum	0.10
7	Khellin	0.5-1.8
8	Water	q.s. to 100 ml

Example 5 - Specific shampoo for problems of the scalp

	INGREDIENTS (INCI names)	% w/v
1	Disodium EDTA	0.10-0.30
2	Polyquaternium-10	0.10-0.30
3	Polyquaternium-55	0.1-0.50
4	Citric acid	0.60-0.80
5	Potassium undecylenoyl hydrolyzed wheat protein	3.6000
6	Sodium lauroyl sarcosinate	1.5000
7	Cocamide mipa	1.0-3.0
8	Disodium laureth sulfosuccinate	1.0-5.0
9	Disodium capryloyl glutamate	0.4-1.0
10	Zinc coceth sulfate	1.0-8.0
11	PEG-200 hydrogenated glyceryl palmate	0.5-3.0
12	PEG-7 glyceryl cocoate	0.5-2.0
13	Laureth-2	0.05-2.0
14	PEG-40 hydrogenated castor oil	0.2-1.0
15	Parfum	q.s.
16	Phenyl trimethicone	0.05-3.0
17	Silicone quaternium-15	0.005-1.0
18	Laureth-4	0.010-0.5
19	Khellin	0.5-1.8
20	Water	q.s. to 100 ml

Example 6 - Hair mousse

	Ingredients (INCI names)	% w/v
1	Alcohol denat.	12.0-15.0
4	Ethoxydiglycol	1.0-3.0
5	Sodium lauryl sulfate	0.5-2.0
6	Sodium hydroxide	0.01-0.06
7	Citric acid	0.01-0.06
8	Peg-40 hydrogenated castor oil	0.30-0.60
9	Parfum	q.s
10	Tocotrienols	0.01-0.05
11	Potassium undecylenoyl hydrolyzed wheat protein	0.050-1.0
12	Zinc coceth sulfate	0.050-0.1
13	Polyquaternium-16	0.020
14	Khellin	0.2-0.5
15	Water	q.s. to 100ml

Example 7 - Liposomal mask for hair

	Components	% w/v
1	Glycerin	3.00
	Ornithine	0.20-0.9
3	Phenylalanine	0.20-0.60
4	Pycnogenol	0.10-0.50
5	Tween 20	1.00
6	Cremophor	0.30
7	Aristoflex	0.70
8	Phenonip	0.98
9	Copper gluconate	0.10
10	Catechin	0.05-0.1
11	Cromollient SCE	3.00
12	Quercetin	0.01-0.1
13	Cremophor	0.60
14	Khellin	0.3-1.3
15	Phosal 75 SA	3.00
16	Parfum	0.60
17	Patent blue (0.2% solution)	0.30
18	Demineralized water	q.s. to 100 ml

Example 8 - Hair mask

	Components	% w/v
1	Corn starch	1.5
2	Ornithine	0.8-1.20
3	Phenylalanine	0.1-0.40
4	Copper gluconate	0.05-0.1
5	BC 2366	2.5
6	Disodium EDTA	0.2
7	Cetrimonium chloride	4
8	Salcare SC 92	2
9	Glycerin	4
10	Nexbase 2004	2
11	Ceramide A2	0.2-0.5
12	Fancol VB	1.5
13	BC 2262	0.5
14	Lanette O	1.5
15	Palm Oil	0.8
16	Brij 721	1
17	Khellin	0.5-1.5
18	Crodazosoft DBQ	8
19	Catechin	0.025-0.07
20	Cremophor RH 40	0.2
21	Tween 20	0.9
22	Glycerin	3.0
23	Panthenol	0.1-0.25
24	Nanocream	0.8-1.2
25	Incroquat behenyl tms	0.5-0.7
26	Quercetin	0.01-0.005
27	Cromollient SCE	0.6
28	Tween 20	0.1
29	Parfum	0.5
30	Phenonip	1
31	Water	q.s. to 100 ml

Example 9 - Shampoo

	Components	% w/v
1	EDTA	0.20
2	Ornithine	0.5-1.2
3	Phenylalanine	0.2-0.6
4	Copper gluconate	0.08-0.12
5	Polyquaternium-10	0.40
6	Sodium Lauroyl Sarcosinate	9.00
7	Magnesium laureth sulfate (75%) and Disodium laureth sulfosuccinate (25%)	38.00
8	Potassium Undecylenoyl Hydrolyzed wheat protein	1.00
9	PEG40 Hydrogenated Castor Oil	0.50
10	Polysorbate 20	1.00
11	Catechin	0.025-0.07
12	Pycnogenol	0.05-0.15
13	Cremophor RH 40	0.2
14	Tween 20	0.9
15	glycerin	3.0
16	panthenol	0.2
17	nanocream	10
18	Quercetin	0.01-0.005
19	cromollient SCE	0.6
20	Prolipid 151	0.6
21	khellin	0.5-1.5
22	tween 20	0.3
23	cremophor RH40	6
24	Phenyltrimethicone & Silicone Quaternium-15	0.50
25	Silicone quaternium-15 & C11-15 Pareth-5 & C11-15 Pareth-9	0.80
26	Parfum 12144	0.60
27	BHA	0.01
28	Crodasilk liquid	1.00
29	Lauryl Methyl Gluceth-10 Hydroxypropyldimonium Chloride	0.50
30	Wheat (triticum vulgare) gliadins	1.00
31	Hairspheres Biogenina	0.2-0.3
32	Dore Gold AS 232	0.05
33	Glycol Distearate, Laureth-7, Sodium Cocoamphoacetate, Cocamidopropyl Betaine and Sodium Laureth Sulfate	6.00
34	PEG-90 Glyceryl Isostearate (and) Laureth-2	1.20
35	PEG-120 Methyl Glucose dioleate	1.20
36	KCI	0.60
37	phenoxyethanol, methylparaben, butylparaben, ethylparaben, propylparaben	0.98
38	citric acid	0.50
39	Demineralized water	q.s. to 100.00 ml

Example 10 - Hair lotion

	INGREDIENTS (INCI names)	g in 100 ml
1	Citric acid	0.04-0.052
2	Disodium EDTA	0.03-0.06
3	Alcohol	15-20
4	PEG-40 Hydrogenated castor oil	0.5-3
5	Tween 20	0.5-1.0
6	Parfum	0.10
7	Khellin	0.5-1.8
8	Ornithine	0.2-0.5
	Water	q.s. to 100 ml

Example 11 - Specific shampoo for problems of the scalp

	INGREDIENTS (INCI names)	% w/v
1	Disodium EDTA	0.10-0.30
2	Polyquaternium-10	0.10-0.30
3	Polyquaternium-55	0.1-0.50
4	Citric acid	0.60-0.80
5	Ornithine	0.10-0.05
6	Potassium undecylenoyl hydrolyzed wheat protein	3.6000
7	Sodium lauroyl sarcosinate	1.5000
8	Cocamide mipa	1.0-3.0
9	Phenylalanine	0.10-0.50
10	Disodium laureth sulfosuccinate	1.0-5.0
11	Disodium capryloyl glutamate	0.4-1.0
12	Zinc coceth sulfate	1.0-8.0
13	Peg-200 hydrogenated glyceryl palmate	0.5-3.0
14	Peg-7 glyceryl cocoate	0.5-2.0
15	Laureth-2	0.05-2.0
16	Peg-40 hydrogenated castor oil	0.2-1.0
17	Parfum	q.s.
18	Phenyl trimethicone	0.05-3.0
19	Silicone quaternium-15	0.005-1.0
20	Laureth-4	0.010-0.5
21	Khellin	0.5-1.8
22	Catechin	0.025-0.07
23	Quercetin	0.01-0.005
24	Water	q.s. to 100 ml

Example 12 - Hair mousse

	Ingredients (INCI names)	% w/v
1	Alcohol denat.	12.0-15.0
2	Ornithine	0.050-0.20
3	Salicylic acid	0.05-0.02
4	Ethoxydiglycol	1.0-3.0
6	Sodium lauryl sulfate	0.5-2.0
7	Sodium hydroxide	0.01-0.06
8	Citric acid	0.01-0.06
9	Panthenol	0.200
10	Glutathione	0.10-0.5
11	P-hydroxyanisole	0.05-0.12
12	Potassium azeloyl diglycinate	0.090
13	Phytic acid	0.01-0.03
14	Peg-40 hydrogenated castor oil	0.30-0.60
15	Parfum	q.b
16	Tocotrienols	0.01-0.05
17	Potassium undecylenoyl hydrolyzed wheat protein	0.050-1.0
18	Zinc coceth sulfate	0.050-0.1
19	Polyquaternium-16	0.020
20	Phenylalanine	0.2-0.6
21	Khellin	0.2-0.5
22	Water	q.s to 100 ml

With the aim of better understanding the advantages of the invention, the following describes a clinical study carried out on healthy volunteers.

CLINICAL STUDY

An assessment was made of the effectiveness of a topical treatment for reducing the amount of white hair due to canities of two compositions in accordance with the invention, i.e.

1) hair mask formulated with liposomes
2) shampoo formulated with liposomes

A double-blind clinical study was carried out using a mask 1-A in accordance with the invention comprising 1.5% w/v khellin in combination with phenylalanine, ornithine, copper gluconate and excipients suitable for topical application to hair, compared with the use of a placebo formulation 1-B, i.e. a similar mask base for hair but without the active principle.
50 volunteers, comprising 40 women and 10 men between 35 and 55 years of age, and healthy according to specific inclusion and exclusion criteria, including the exclusion of immunological pathologies and of systemic drug consumption were treated as follows.
1-A and 1-B were applied three times a week for eight weeks to each subject. At the end of the treatment, each subject was evaluated by:

dermatological examination
macro photograph (digital)
epiluminescence (Molemax II)
Reflectance Confocal Microscopy (RCM) using a Lucid confocal microscope.

In 65% of the subjects treated with mask 1-A a 20-30% reduction in grey/white hair was found compared with a 2% reduction in grey/white hair in subjects treated with mask 1-B, with reduction of up to a maximum of 5%, p = 0.05.
Additionally, of those treated with mask 1-A, an increase in the anagen phase of the hair growth cycle (compared to the baseline) as well as an increase in the hair shaft diameter were found in subjects affected by androgenetic alopecia.
After having completed the assessment on the treatment with mask 1), the subjects in active group A used a gentle shampoo 2-A containing 1% khellin and formulated with liposomes, to be used twice weekly for four weeks.
The subjects in non-active group B used a normal gentle shampoo 2-B as a comparison, i.e. without active principles.
At the end of the four weeks, the assessments were repeated on all subjects.

in group A it was found that the results obtained with mask 1-A application were maintained.
in group B with free shampoo 2-B a slight increase in grey hair was noted, but was not statistically significant compared to the baseline of the non-active group. In conclusion, application of mask 1-A with the active principle of the invention has demonstrated a capacity to increase the number of repigmented hairs even though repigmentation of the whole head of hair was not observed.

Application of shampoo 2-A was shown to be effective in maintaining the action of mask 1-A treatment.
No systemic or localized side effects were noted on use of the products at the end of the reported study.
The composition of the invention is mainly indicated for anti-ageing cosmetic use, for preventing and treating canities and hence ageing of the hair.
It is particularly indicated for the treatment of greying hair and hair in the initial stages of canities for reducing its progression.
Following topical application of the composition of the invention to hair, an increase in the anagen phase of the hair growth cycle (compared to the baseline) as well as an increase in hair shaft diameter in subjects affected by androgenetic alopecia was generally also apparent.
For this reason, the composition of the invention is particularly indicated for the treatment of canities associated with androgenetic alopecia.

Claims

Use of khellin as a cosmetic for reducing the amount of grey or white hair due to canities.
Use of khellin for reducing the amount of grey or white hair due to canities, while at the same time producing an increase in the anagen phase and hair shaft diameter in subjects affected by androgenetic alopecia.
Use according to the preceding claims wherein khellin is formulated in a composition comprising excipients suitable for topical use on hair.
Use according to the preceding claims wherein khellin is used in combination with one or more active compounds chosen from: phenylalanine, ornithine, catechin, quercetin, copper salts.
Use according to the preceding claims wherein khellin is prepared in the form of a mask for hair treatment, or shampoo, or lotion, or conditioner, or mousse.
Use according to claim 5 wherein the said form contains liposomes.
Use according to the preceding claims wherein khellin is prepared in a composition in a quantity from 0.2 to 1.8% w/v.